Low vitamin K status, high sclerostin and mortality risk of stable coronary heart disease patients.

Aim: We explored whether matrix Gla protein (MGP, natural calcification inhibitor) and sclerostin (glycoprotein responsible for osteoblast differentiation) interact in terms of mortality risk in coronary patients. Methods: 945 patients after myocardial infarction and/or coronary revascularization were followed in a prospective study. All-cause death, fatal or nonfatal cardiovascular events and heart failure hospitalizations were registered. Results: Either high desphospho-uncarboxylated MGP (dp-ucMGP) or high sclerostin were independently associated with 5-year all-cause/cardiovascular mortality. However, we observed an additional mortality risk in the coincidence of both factors. Concomitantly high dp-ucMGP (≥884 pmol/l) plus sclerostin (≥589 ng/l) were associated with increased all-cause mortality risk compared with 'normal' concentrations of both factors (HRR 3.71 [95% CI: 2.07-6.62, p < 0.0001]), or if only one biomarker has been increased. A similar pattern was observed for fatal, but not for nonfatal cardiovascular events. Conclusion: Concomitantly high MGP and sclerostin indicate increased mortality risk, which probably reflects their role in cardiovascular calcifications.

The coincidence of low vitamin K status and high expression of growth differentiation factor 15 may indicate increased mortality risk in stable coronary heart disease patients.

BACKGROUND AND AIMS: Matrix Gla protein (MGP) is a natural inhibitor of vascular calcification critically dependent on circulating vitamin K status. Growth differentiation factor 15 (GDF-15) is a regulatory cytokine mainly of the inflammatory and angiogenesis pathways, but potentially also involved in bone mineralization. We sought to determine whether these two circulating biomarkers jointly influenced morbidity and mortality risk in patients with chronic coronary heart disease (CHD). METHODS AND RESULTS: 894 patients ≥6 months after myocardial infarction and/or coronary revascularization at baseline were followed in a prospective study. All-cause and cardiovascular mortality, non-fatal cardiovascular events (myocardial infarction, stroke, any revascularization), and hospitalization for heart failure (HF) were followed as outcomes. Desphospho-uncarboxylated MGP (dp-ucMGP) was used as a biomarker of vitamin K status. Both, increased concentrations of dp-ucMGP (≥884 pmol/L) and GDF-15 (≥1339 pg/mL) were identified as independent predictors of 5-year all-cause or cardiovascular mortality. However, their coincidence further increased mortality risk. The highest risk was observed in patients with high dp-ucMGP plus high GDF-15, not only when compared with those with "normal" concentrations of both biomarkers [HR 5.51 (95% CI 2.91-10.44), p < 0.0001 and 6.79 (95% CI 3.06-15.08), p < 0.0001 for all-cause and cardiovascular mortality, respectively], but even when compared with patients with only one factor increased. This pattern was less convincing with non-fatal cardiovascular events or hospitalization for HF. CONCLUSIONS: The individual coincidence of low vitamin K status (high dp-ucMGP) and high GDF-15 expression predicts poor survival of stable CHD patients.

The Prognostic Importance of Impaired Fasting Glycemia in Chronic Coronary Heart Disease Patients.

OBJECTIVES: Impaired glucose metabolism represents one the most important cardiovascular risk factors, with steeply raising prevalence in overall population. We aimed to compare mortality risk of impaired fasting glycaemia (IFG) and overt diabetes mellitus (DM) in patients with coronary heart disease (CHD). STUDY DESIGN: prospective cohort study METHODS: A total of 1685 patients, 6-24 months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. Overt DM was defined as fasting glucose ≥ 7 mmol/L and/or use of antidiabetic treatment, while IFG as fasting glucose 5.6-6.99 mmol/L, but no antidiabetic medication. The main outcomes were total and cardiovascular mortality during 5 years of follow-up. RESULTS: During follow-up of 1826 days, 172 patients (10.2%) deceased, and of them 122 (7.2%) from a cardiovascular cause. Both exposures, overt DM (n=623, 37.0% of the whole sample) and IFG (n=436, 25.9%) were associated with an independent increase of 5-year total mortality, compared to normoglycemic subjects [fully adjusted hazard risk ratio (HRR) 1.63 (95%CI: 1.01-2.61)]; p=0.043 and 2.25 (95%CI: 1.45-3.50); p<0.0001, respectively]. In contrast, comparing both glucose disorders one with each other, no significant differences were found for total mortality [HRR 0.82 (0.53-1.28); p=0.33]. Taking 5-years cardiovascular mortality as outcome, similar pattern was observed [HRR 1.96 (95%CI: 1.06-3.63) and 3.84 (95%CI: 2.19-6.73) for overt DM and IFG, respectively, with HRR 0.63 (95%CI: 0.37-1.07) for comparison of both disorders]. CONCLUSIONS: Impaired fasting glycaemia adversely increases mortality of CHD patients in the same extent as overt DM.

Is There Really an Association of High Circulating Adiponectin Concentration and Mortality or Morbidity Risk in Stable Coronary Artery Disease?

Adiponectin has several beneficial properties, namely, on the level of glucose metabolism, but paradoxically, its high concentrations were associated with increased mortality. We aimed to clarify the impact of high serum adiponectin on mortality and morbidity in patients with stable coronary artery heart disease (CAD). A total of 973 patients after myocardial infarction and/or coronary revascularization were followed in a prospective cohort study. All-cause and cardiovascular (CV) death, non-fatal cardiovascular events, and hospitalizations for heart failure (HF) were registered as outcomes. High serum adiponectin levels (≥8.58 ng/ml, i. e., above median) were independently associated with increased risk of 5-year all-cause, CV mortality or HF [with HRR 1.57 (95% CI: 1.07-2.30), 1.74 (95% CI: 1.08-2.81) or 1.94 (95% CI: 1.20-3.12), respectively] when adjusted just for conventional risk factors. However, its significance disappeared if brain natriuretic peptide (BNP) was included in a regression model. In line with this, we observed strong collinearity of adiponectin and BNP. Additionally, major adverse cardiovascular event (i. e., CV death, non-fatal myocardial infarction or stroke, coronary revascularization) incidence risk was not associated with high adiponectin. In conclusion, the observed inverse association between adiponectin concentrations and mortality risk seems to be attributable to concomitantly increased BNP, rather than high adiponectin being a causal factor.

The prognostic importance of subclinical heart failure in stable coronary heart disease patients.

Background: In stable coronary heart disease (CHD) patients we aimed to assess the predictive potential of only mild increase of brain natriuretic peptide (BNP) in subjects free from symptoms or diagnostic criteria of heart failure (HF).Methods: We examined 967 patients, at least 6 months after myocardial infarction or coronary revascularization and divided them into three categories: 'overt HF' (NYHA II-IV, objective signs of HF, chronic treatment with furosemide and/or spironolactone or history of hospitalisation for HF), 'subclinical HF (BNP over 150 ng/mL, but no criterion of overt HF)' and 'no HF' (no above mentioned criterion present). Follow-up was done to assess 5-years all-cause mortality.Results: Overt and subclinical HF (by definition) had 38.8% and 9.6% of patients, respectively. In analyses adjusted for classical risk factors and other possible covariates, both overt and subclinical HF were independently associated with increased mortality compared to no HF subjects [hazard risk ratio 1.99 (95%CI:1.02-3.91) and 3.01 (95%CI:1.90-4.78), respectively. The risk of total mortality was similar in overt and subclinical HF patients [HRR 1.30 (95%CI: 0.72-2.36)]. Within overt HF group, those with BNP >150 ng/mL had also higher mortality risk than those with low BNP levels [HRR 2.79 (95%CI: 1.67-4.68)]. The addition of left ventricle ejection fraction into definition of HF groups did not affect main results.Conclusions: Mild increase of BNP in generally stable and asymptomatic CHD patients identifies high individual mortality risk in the same extend that presence of clinically manifest HF.

Mood disorders impaired quality of life but not the mortality or morbidity risk in stable coronary heart disease patients.

Background: It was suggested that depression and anxiety might be associated with increased cardiovascular risk in both primary and secondary prevention. In stable coronary heart disease (CHD) patients, we aimed to assess prevalence of depression and anxiety, its relations to conventional risk profile and mortality or morbidity and to quality of life (QoL).Methods: We examined 969 patients, at least 6 months after myocardial infarction or coronary revascularisation. Depression or anxiety was assessed using a standard HADS (Hospital Anxiety and Depression Scale), while QoL by SF-36 (Short-Form-36 Questions) questionnaires. Follow-up was done to assess mortality in incidence of non-fatal cardiovascular event.Results: Both mood disorders were rather frequent; borderline depression or anxiety (HADS score 8-10) had 14.8 or 10.9% of patients, respectively; moderate-to-severe depression or anxiety (HADS score ≥11) had another 8.2 or 6.7% of patients. After adjustment for potential covariates impaired QoL (SF-36 score <40) was independently associated with depressive mood [odds ratio (OR) 6.08 (95%CI: 2.92-12.7) or anxiety [OR 8.66 (95%CI: 3.77-19.89)], as well as with combination of both disorders [OR 33.58 (95%CI: 15.5-72.6)]. Conventional risk characteristics remained virtually unrelated to mood disorders (with exception of angina pectoris). We found significantly higher incidence of major cardiovascular events in patients with anxious mood and marginally significant inferior survival in patients with depression, but any cardiovascular risk disappeared if adjusted for potential covariates (conventional risk factors, natriuretic peptides, angina pectoris.)Conclusions: Mood disorders severely affected QoL of stable CHD patients, but not their global cardiovascular risk.

To what extent can the chosen blood pressure measurement technique affect the outcomes of an observational survey?

Aim: We analyzed to what extent measurement protocol influenced individual blood pressure (BP) and achievement of treatment target in patients with coronary heart disease. Methods: In a subsample of Czech EUROASPIRE III-V survey participants (n = 913), we compared the per-protocol BP measurement (by automated oscillometric device OMRON at the beginning of survey procedure) with control auscultatory measurement (by physician during interview). Results: Per-protocol approach produced significantly (p < 0.0001) higher BP values (by 9/6 mmHg in median) than auscultatory measurements and led to markedly higher proportion of patients over target BP (less than 140/90 mmHg; 59.3 vs 34.9% [p < 0.0001], per-protocol vs auscultatory technique, respectively). Conclusion: Per-protocol oscillometric technique was not equivalent to conventional auscultatory measurement and seriously over-rated the real nonachievement of BP target in observational surveys.